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Steven M. Holland - One of the best experts on this subject based on the ideXlab platform.
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risk factors for Disseminated Coccidioidomycosis united states
Emerging Infectious Diseases, 2017Co-Authors: John N Galgiani, Camila D Odio, Beatriz E Marciano, Steven M. HollandAbstract:Of 150,000 new Coccidioidomycosis infections that occur annually in the United States, ≈1% disseminate; one third of those cases are fatal. Immunocompromised hosts have higher rates of dissemination. We identified 8 patients with Disseminated Coccidioidomycosis who had defects in the interleukin-12/interferon-γ and STAT3 axes, indicating that these are critical host defense pathways.
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hospitalizations associated with Disseminated Coccidioidomycosis arizona and california usa
Emerging Infectious Diseases, 2012Co-Authors: Amy E Seitz, Rebecca D Prevots, Steven M. HollandAbstract:We analyzed hospitalization databases from Arizona and California for Disseminated Coccidioidomycosis–associated hospitalizations among immunocompetent persons. Racial/ethnic disease ratios were characterized by a higher incidence of hospitalization among blacks compared with other groups. This finding suggests that HIV infection, AIDS, and primary immune conditions are not a major factor in this disparity.
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two cases illustrating successful adjunctive interferon γ immunotherapy in refractory Disseminated Coccidioidomycosis
Journal of Infection, 2011Co-Authors: Christopher Duplessis, Braden R Hale, Mary Bavaro, Drake H Tilley, Steven M. HollandAbstract:Protective immunity and host resistance to Coccidioidomycosis require a robust cell-mediated immunity with adequate production of Th1 cytokines including interleukin-12, and IFN-γ and appropriate regulation and coordinated functionality of Th1/Th2 responses and IL-12/IFN-γ cytokine axes. IFN-γ augments the anti-fungal activity of effector immune cells against a variety of fungi. Numerous animal models have demonstrated the potential efficacy of adjunctive IFN-γ in treatment of invasive mycoses. Yet, despite these promising data, a paucity of literature documents efficacious adjunctive IFN-γ administration in refractory Coccidioidomycosis. We present two cases of refractory disease occurring at our institution who responded to adjunctive IFN-γ.
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refractory Disseminated Coccidioidomycosis and mycobacteriosis in interferon γ receptor 1 deficiency
Clinical Infectious Diseases, 2009Co-Authors: Donald C Vinh, John N Galgiani, Fares Masannat, Robert B Dzioba, Steven M. HollandAbstract:Severe Coccidioidomycosis is rare, and specific genetic susceptibility to the disease remains unidentified. We describe a patient with Disseminated recalcitrant Coccidioidomycosis with autosomal dominant interferon-gamma receptor 1 deficiency caused by a heterozygous IFNGR1 818del4 mutation. Therefore, the interleukin-12/interferon-gamma axis appears to be critical for control of Coccidioidomycosis.
John N Galgiani - One of the best experts on this subject based on the ideXlab platform.
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natural history of Disseminated Coccidioidomycosis examination of the va armed forces database
Clinical Infectious Diseases, 2020Co-Authors: Derek J Bays, George Richard Thompson, Susan E Reef, Linda Snyder, Alana J Freifeld, Milt Huppert, David Salkin, Machelle D Wilson, John N GalgianiAbstract:BACKGROUND The natural history of non-central nervous system (CNS) Disseminated Coccidioidomycosis (DCM) has not been previously characterized. The historical VA-Armed Forces Coccidioidomycosis patient group provides a unique cohort of patients not treated with standard antifungal therapy allowing for characterization of the natural history of Coccidioidomycosis. METHODS We conducted a retrospective study of 531 VA-Armed Forces Coccidioidomycosis patients diagnosed between 1955-1958 and followed to 1966. Groups were identified as non-Disseminated Coccidioidomycosis (non-DCM, 462 patients), DCM (44 patients), and CNS (25 patients). The duration of initial infection, fate of primary infection, all-cause mortality and mortality secondary to Coccidioidomycosis were assessed and compared between groups. RESULTS Mortality due to Coccidioidomycosis at last known follow up was significantly different across the groups: 0.65% in non-DCM, 25% in DCM, and 88% in CNS (P<0.001). The primary fate of pulmonary infection demonstrated key differences with pulmonary nodules observed in 39.61% in non-DCM, 13.64% in DCM, and 20% in CNS (P<0.001). There were differences in cavity formation with 34.20% in non-DCM, 9.09% DCM, and 8 % in CNS (P <0.001). Forty-one percent and 56% of patients in the non-CNS DCM and CNS groups, respectively, developed dissemination as the presenting manifestation or concurrent with initial infection. CONCLUSIONS This large retrospective cohort study helps characterize the natural history of DCM, provides insight into the host immunologic response, and has direct clinical implications for the management and follow-up of patients.
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risk factors for Disseminated Coccidioidomycosis united states
Emerging Infectious Diseases, 2017Co-Authors: John N Galgiani, Camila D Odio, Beatriz E Marciano, Steven M. HollandAbstract:Of 150,000 new Coccidioidomycosis infections that occur annually in the United States, ≈1% disseminate; one third of those cases are fatal. Immunocompromised hosts have higher rates of dissemination. We identified 8 patients with Disseminated Coccidioidomycosis who had defects in the interleukin-12/interferon-γ and STAT3 axes, indicating that these are critical host defense pathways.
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refractory Disseminated Coccidioidomycosis and mycobacteriosis in interferon γ receptor 1 deficiency
Clinical Infectious Diseases, 2009Co-Authors: Donald C Vinh, John N Galgiani, Fares Masannat, Robert B Dzioba, Steven M. HollandAbstract:Severe Coccidioidomycosis is rare, and specific genetic susceptibility to the disease remains unidentified. We describe a patient with Disseminated recalcitrant Coccidioidomycosis with autosomal dominant interferon-gamma receptor 1 deficiency caused by a heterozygous IFNGR1 818del4 mutation. Therefore, the interleukin-12/interferon-gamma axis appears to be critical for control of Coccidioidomycosis.
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fluconazole in the treatment of chronic pulmonary and nonmeningeal Disseminated Coccidioidomycosis
The American Journal of Medicine, 1995Co-Authors: Antonino Catanzaro, John N Galgiani, Bernard E Levine, Joshua Fierer, David A Stevens, Patricia K Sharkeymathis, Stanley W Chapman, Gretchen A CloudAbstract:Purpose To determine the efficacy and safety of fluconazole as treatment for Coccidioidomycosis. Patients and methods This was a multiCenter, open-label, single-arm study. Of 78 patients enrolled, 22 had soft-tissue, 42 had chronic pulmonary, and 14 had skeletal Coccidioidomycosis. Forty-nine had at least one concomitant disease, 7 of whom had HIV infection. Patients were given oral fluconazole 200 mg/d. Nonresponders were increased to 400 mg/d. Treatment courses were long: a mean of 323 ±230 days at 200 mg and 433 ± 178 days at 400 mg. Predefined assessment of disease-related abnormalities was performed at the time of enrollment and repeated at least every 4 months. A satisfactory response was defined as any reduction of baseline abnormality by month 4 and at least 51% reduction by month 8. Results Among 75 evaluable patients, a satisfactory response was observed in 12 (86%) of the 14 patients with skeletal, 22 (55%) of the 40 patients with chronic pulmonary, and 16 (76%) of the 21 patients with soft-tissue disease. Five patients (7%) required modification of treatment due to toxicity. Forty-one patients who responded were followed off drug. Fifteen (37%) of them experienced reactivation of infection. Conclusion Fluconazole 200 or 400 mg/d is well tolerated and a moderately effective treatment for chronic pulmonary or nonmeningeal Disseminated Coccidioidomycosis. The relapse rate following therapy is high. Treatment trials with higher doses appear warranted. The relative efficacy of fluconazole versus other azoles or amphotericin B remains unknown.
Neil M Ampel - One of the best experts on this subject based on the ideXlab platform.
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cytokine and anticytokine therapy for Disseminated Coccidioidomycosis
NEJM Journal Watch, 2020Co-Authors: Neil M AmpelAbstract:A 4-year-old child was found to have multisite Disseminated Coccidioidomycosis that was unresponsive to antifungal therapy and only partially
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cytokine profiles from antigen stimulated whole blood samples among patients with pulmonary or nonmeningeal Disseminated Coccidioidomycosis
Clinical and Vaccine Immunology, 2015Co-Authors: Neil M Ampel, Suzanne M Johnson, Lance Nesbit, Chinh Nguyen, Suzette Chavez, Kenneth S Knox, Demosthenes PappagianisAbstract:The outcome of Coccidioidomycosis depends on a robust specific cellular immune response. A T-helper type 1 (Th1) cellular immune response has been previously associated with resolution of clinical illness. However, the precise elements of this response and whether cytokines not involved with the Th1 response play a role in Coccidioidomycosis are not known. Whole-blood samples were obtained from subjects with active Coccidioidomycosis and controls and incubated for 18 h with T27K, a coccidioidal antigen preparation. The supernatant was then assayed for gamma interferon (IFN-γ), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, IL-10, and IL-17A. A total of 43 subjects, 16 with acute pneumonia, 9 with pulmonary sequelae of nodules and cavities, and 18 with nonmeningeal Disseminated Coccidioidomycosis, were studied. Compared to concentrations in healthy immune and nonimmune donors, the median concentration of IL-17A was significantly higher in those with active Coccidioidomycosis (for both, P < 0.01). In addition, IL-6 concentrations were higher while IL-2 and IFN-γ concentrations were significantly lower in those with nonmeningeal Disseminated disease diagnosed within 12 months than in those with acute pneumonia (for all, P < 0.05). The cytokine profile among patients with active Coccidioidomycosis is distinct in that IL-17A is persistently present. In addition, those with nonmeningeal Disseminated disease have an increased inflammatory cytokine response and diminished Th1 responses that modulate over time.
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Coccidioidomycosis during pregnancy a review and recommendations for management
Clinical Infectious Diseases, 2011Co-Authors: Robert Bercovitch, Neil M Ampel, Antonino Catanzaro, Demosthenes Pappagianis, Brian S Schwartz, Heather D WattsAbstract:Pregnancy is an established risk factor for the development of severe and Disseminated Coccidioidomycosis, particularly when infection is acquired during the later stages of gestation. Although recent studies suggest that the incidence of symptomatic Coccidioidomycosis during pregnancy is decreasing and that outcome has improved, management is complicated by the observations that azole antifungal agents can be teratogenic when given to some women, particularly at high doses, early in pregnancy. This article summarizes the data on these issues and offers guidance on the management of Coccidioidomycosis during pregnancy.
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in vitro whole blood analysis of cellular immunity in patients with active Coccidioidomycosis by using the antigen preparation t27k
Clinical and Vaccine Immunology, 2002Co-Authors: Neil M Ampel, Larissa A Kramer, Deborah S Carroll, K M Kerekes, Suzanne M Johnson, Demosthenes PappagianisAbstract:Measurement of cellular immunity in human Coccidioidomycosis has important diagnostic and prognostic implications. The coccidioidin skin test has been the standard for the measurement of this, but it is not available in the United States. We examined the utility of measuring surface expression of CD69 on T lymphocytes in whole blood incubated with the coccidioidal antigen preparation T27K as an alternative to the skin test. Seventy donors with active Coccidioidomycosis were studied. The mean fluorescent intensity (MFI) of CD69 expression on CD3 lymphocytes in response to T27K was 28.61 ± 1.77, significantly greater than the control response of 11.45 ± 0.78 (P < 0.001). The MFI CD69 response to T27K above that for the control (MFI CD69 above control) was 6.35 ± 2.18 for seven subjects with Disseminated Coccidioidomycosis who were studied within 5 months of diagnosis. This was significantly below the value of 20.17 ± 3.17 for 18 subjects with pulmonary Coccidioidomycosis studied within 5 months of diagnosis and the value of 19.58 ± 2.91 for 27 subjects with Disseminated Coccidioidomycosis studied after 5 months of diagnosis (for both, P < 0.05). There was an inverse correlation between coccidioidal clinical score and MFI CD69 above control for all 34 subjects with Disseminated Coccidioidomycosis (r = 0.362; P = 0.036) but not for the 36 subjects with pulmonary disease (r < 0.001; P = 0.993). Among 30 subjects for whom data were available, there was a highly significant association between the MFI CD69 above control and the supernatant concentrations of gamma interferon, interleukin-2 (IL-2), and tumor necrosis factor alpha (for all, P < 0.001), but not for IL-4, IL-5, or IL-10. These data indicate that in vitro assessment of CD69 expression on T lymphocytes by using T27K may be a useful measure of cellular immune response among subjects with active Coccidioidomycosis.
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reversal of coccidioidal anergy in vitro by dendritic cells from patients with Disseminated Coccidioidomycosis
Journal of Immunology, 2002Co-Authors: John O Richards, Neil M Ampel, Douglas F LakeAbstract:Coccidioides immitis is a pathogenic, dimorphic fungus found in the southwestern United States and is the causative agent of Coccidioidomycosis. Extrathoracic dissemination of Coccidioidomycosis is associated with a lack of cellular immunity. Dendritic cells (DCs) have been shown to initiate and modulate cellular immune responses. To determine whether DCs could modulate or initiate the immune response in this disease, monocyte-derived DCs were generated from coccidioidal Ag nonresponsive patients with Disseminated Coccidioidomycosis and healthy nonimmune individuals. DCs generated from both groups demonstrated phenotypes characteristic of DCs and stimulated strong allogeneic MLR. DCs from patients and healthy nonimmune individuals pulsed with the coccidioidal Ag preparation T27K induced lymphocyte proliferation. Mature DCs were much more efficient than immature DCs in these stimulations. Furthermore, restimulation of T27K-primed PBMC with Ag-pulsed DCs generated a C. immitis-specific cellular immune response in PBMC from patients with Disseminated Coccidioidomycosis as well as healthy nonimmune individuals. These results show that 1) DCs have the capacity to stimulate specific cellular immune responses from patients with Disseminated Coccidioidomycosis who are nonresponsive to coccidioidal Ag and healthy nonimmune individuals in vitro; 2) DCs can be used to screen coccidioidal Ags as candidates for human vaccine development; and 3) DC therapy may be useful in the treatment of Disseminated Coccidioidomycosis.
Demosthenes Pappagianis - One of the best experts on this subject based on the ideXlab platform.
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cytokine profiles from antigen stimulated whole blood samples among patients with pulmonary or nonmeningeal Disseminated Coccidioidomycosis
Clinical and Vaccine Immunology, 2015Co-Authors: Neil M Ampel, Suzanne M Johnson, Lance Nesbit, Chinh Nguyen, Suzette Chavez, Kenneth S Knox, Demosthenes PappagianisAbstract:The outcome of Coccidioidomycosis depends on a robust specific cellular immune response. A T-helper type 1 (Th1) cellular immune response has been previously associated with resolution of clinical illness. However, the precise elements of this response and whether cytokines not involved with the Th1 response play a role in Coccidioidomycosis are not known. Whole-blood samples were obtained from subjects with active Coccidioidomycosis and controls and incubated for 18 h with T27K, a coccidioidal antigen preparation. The supernatant was then assayed for gamma interferon (IFN-γ), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, IL-10, and IL-17A. A total of 43 subjects, 16 with acute pneumonia, 9 with pulmonary sequelae of nodules and cavities, and 18 with nonmeningeal Disseminated Coccidioidomycosis, were studied. Compared to concentrations in healthy immune and nonimmune donors, the median concentration of IL-17A was significantly higher in those with active Coccidioidomycosis (for both, P < 0.01). In addition, IL-6 concentrations were higher while IL-2 and IFN-γ concentrations were significantly lower in those with nonmeningeal Disseminated disease diagnosed within 12 months than in those with acute pneumonia (for all, P < 0.05). The cytokine profile among patients with active Coccidioidomycosis is distinct in that IL-17A is persistently present. In addition, those with nonmeningeal Disseminated disease have an increased inflammatory cytokine response and diminished Th1 responses that modulate over time.
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Coccidioidomycosis during pregnancy a review and recommendations for management
Clinical Infectious Diseases, 2011Co-Authors: Robert Bercovitch, Neil M Ampel, Antonino Catanzaro, Demosthenes Pappagianis, Brian S Schwartz, Heather D WattsAbstract:Pregnancy is an established risk factor for the development of severe and Disseminated Coccidioidomycosis, particularly when infection is acquired during the later stages of gestation. Although recent studies suggest that the incidence of symptomatic Coccidioidomycosis during pregnancy is decreasing and that outcome has improved, management is complicated by the observations that azole antifungal agents can be teratogenic when given to some women, particularly at high doses, early in pregnancy. This article summarizes the data on these issues and offers guidance on the management of Coccidioidomycosis during pregnancy.
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donor related Coccidioidomycosis in organ transplant recipients
Clinical Infectious Diseases, 2003Co-Authors: Patty W Wright, Demosthenes Pappagianis, Kenneth Komatsu, Mark Wilson, Ana Paula Louro, Stephen A Moser, Peter G PappasAbstract:Most cases of Coccidioidomycosis in organ transplant recipients arise from either primary infection with Coccidioides immitis after environmental exposure or from reactivation of latent infection. Herein, we report 2 cases of rapidly fatal, Disseminated Coccidioidomycosis that occurred in organ transplant recipients who had never lived in or visited an area where C. immitis is endemic. Both subjects had received a transplanted organ from the same donor, an individual with unrecognized active Coccidioidomycosis at the time of his death.
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in vitro whole blood analysis of cellular immunity in patients with active Coccidioidomycosis by using the antigen preparation t27k
Clinical and Vaccine Immunology, 2002Co-Authors: Neil M Ampel, Larissa A Kramer, Deborah S Carroll, K M Kerekes, Suzanne M Johnson, Demosthenes PappagianisAbstract:Measurement of cellular immunity in human Coccidioidomycosis has important diagnostic and prognostic implications. The coccidioidin skin test has been the standard for the measurement of this, but it is not available in the United States. We examined the utility of measuring surface expression of CD69 on T lymphocytes in whole blood incubated with the coccidioidal antigen preparation T27K as an alternative to the skin test. Seventy donors with active Coccidioidomycosis were studied. The mean fluorescent intensity (MFI) of CD69 expression on CD3 lymphocytes in response to T27K was 28.61 ± 1.77, significantly greater than the control response of 11.45 ± 0.78 (P < 0.001). The MFI CD69 response to T27K above that for the control (MFI CD69 above control) was 6.35 ± 2.18 for seven subjects with Disseminated Coccidioidomycosis who were studied within 5 months of diagnosis. This was significantly below the value of 20.17 ± 3.17 for 18 subjects with pulmonary Coccidioidomycosis studied within 5 months of diagnosis and the value of 19.58 ± 2.91 for 27 subjects with Disseminated Coccidioidomycosis studied after 5 months of diagnosis (for both, P < 0.05). There was an inverse correlation between coccidioidal clinical score and MFI CD69 above control for all 34 subjects with Disseminated Coccidioidomycosis (r = 0.362; P = 0.036) but not for the 36 subjects with pulmonary disease (r < 0.001; P = 0.993). Among 30 subjects for whom data were available, there was a highly significant association between the MFI CD69 above control and the supernatant concentrations of gamma interferon, interleukin-2 (IL-2), and tumor necrosis factor alpha (for all, P < 0.001), but not for IL-4, IL-5, or IL-10. These data indicate that in vitro assessment of CD69 expression on T lymphocytes by using T27K may be a useful measure of cellular immune response among subjects with active Coccidioidomycosis.
Simon Paul - One of the best experts on this subject based on the ideXlab platform.
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immune reconstitution inflammatory syndrome in patients with aids and Disseminated Coccidioidomycosis a case series and review of the literature
Journal of the International Association of Providers of AIDS Care, 2017Co-Authors: Thwe Thwe Shein, Priya Jayachandran, Simon PaulAbstract:Coccidioidomycosis causes substantial morbidity and mortality in endemic areas, and dissemination is frequent in patients with impaired cellular immunity such as AIDS. Immune reconstitution inflammatory syndrome (IRIS) is paradoxical clinical worsening after initiation of antiretroviral therapy (ART) in a patient with HIV and a simultaneous opportunistic infection (OI). Immune reconstitution inflammatory syndrome has been well described for a host of mycobacterial, viral, and fungal OIs and malignancies such as Kaposi sarcoma. To date, only 3 cases of IRIS due to Coccidioidomycosis have been reported in the literature. At our institution, we report 4 cases of IRIS in HIV-infected patients with Disseminated Coccidioidomycosis. Unfortunately, all 4 patients died of worsening coccidioidal infection after initiating ART. The optimal timing of ART in patients with AIDS and Coccidioidomycosis remains to be elucidated.
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sertraline demonstrates fungicidal activity in vitro for coccidioides immitis
Mycology, 2016Co-Authors: Simon Paul, Roger B Mortimer, Marilyn MitchellAbstract:ABSTRACTCoccidioidomycosis causes substantial morbidity in endemic areas. Disseminated Coccidioidomycosis is an AIDS defining condition and treatment often requires lifelong antifungal therapy. Sertraline, a widely used serotonin-reuptake inhibitor anti-depressant, has demonstrated activity against Candida and Cryptococcus sp. both in vitro and in vivo. To evaluate if sertraline has activity against Coccidioides, the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of sertraline for four clinical isolates of C. immitis were determined. Sertraline was observed to have an MIC range of 4–8 µg/ml and MFC also of 4–8 µg/ml for Coccidioides. These MIC and MFC results for C. immitis are similar to those reported for Cryptococcus sp. suggesting sertraline may potentially have utility for the treatment of Coccidioidomycosis.